Killing Two Birds With One Stone: Successful Management With Rituximab in the Coexistence of Myasthenia Gravis and Marginal Zone Lymphoma.

Myasthenia gravis (MG) is an autoimmune neuromuscular disorder characterized by motor weakness affecting various muscle groups. The simultaneous or sequential occurrence of lymphoma and MG, often seen in patients, could be influenced by common genetic and biological factors that drive unregulated lymphocyte growth, leading to autoimmunity and lymphoma. This case report describes a 72-year-old male with coexisting marginal zone lymphoma and MG, who exhibited a positive response to rituximab treatment intended for the lymphoma, but surprisingly effective for both conditions. The patient experienced significant improvement in MG symptoms and a decline in serum anti-acetylcholine receptor (AChR) antibodies, along with achieving hematologic remission in the lymphoma. These observations emphasize the potential therapeutic advantages of rituximab in treating cases with concurrent MG and lymphoma, providing useful insights for future research and multifaceted clinical management.

Chemotherapy-induced coronary arteries calcium score deterioration as detected with unenhanced CT portion of FDG PET/CT.

This study aims to detect the potential impact of chemotherapy on the coronary calcium scoring (CCS) in lymphoma patients undergoing FDG-PET/CT at baseline and for therapy response using the CT portion of the exam to calculate the CCS. One hundred twelve lymphoma patients were included in the study based on having both baseline and at least 2 post-chemotherapy scans. The unenhanced CT portions of the scans were reviewed to measure the CCS which was then extracted using the Toshiba Vital Program. Agatston scores were assessed as category 1 with zero CCS unit and categories 2 to 5 having more than >1, 11, 101, and 400 CCS units respectively. For statistical analysis, paired T-Tests were used to compare results. The overall changes in total coronary artery calcium (CAC) from baseline to last treatment showed a statistically significant increase in CAC with an average increase of at least 35% in the CAC score. We also compared the overall changes in CAC with patients having category 1 and 2 Agatston at baseline and found no statistical increase in CAC post-chemotherapy. Additionally, we compared the overall changes in CAC with patients having category 3 and 4 Agatston at baseline and found statistically significant increase in CAC post-chemotherapy. In lymphoma patients, chemotherapy may cause worsening of CCS and this can serve as an early indicator of chemotherapy-induced cardiac toxicity. When present, such CCS deterioration can be detected by the unenhanced CT portion of routine oncologic FDG PET/CT scans.

Acute myeloid leukemia induction with cladribine: Outcomes by age and leukemia risk.

Acute myeloid leukemia (AML) induction traditionally includes seven days of cytarabine and three days of an anthracycline (7 + 3). Because of evidence of increased efficacy of cladribine combined with this regimen, we conducted a retrospective analysis of 107 AML patients treated with idarubicin, cytarabine and cladribine (IAC) at our institution. Complete remission (CR) occurred in 71%, with overall response of 79%. One-year survival overall was 59%, with 47% (27/57) among patients ≥60 years old and 72% (36/50) in those <60 (Relative Risk [RR] 1.9, 95% CI 1.2-3.2). Median overall survival was 17.3 months in all patients and Cox proportional hazard ratio (HR) for death was 2.2 (95% CI 1.3-3.6) for age ≥60 years compared to <60 years. One year survival was 100% among favorable NCCN risk patients versus 64% in intermediate-risk and 35% in poor-risk patients (p < 0.001). HR for death in intermediate- risk (4.2, 95% CI 1.5-12) and poor-risk (8.4, 95% CI 3.0-24) compared to favorable risk AML was higher than that associated with age ≥60 years (HR 2.2). We conclude that IAC is an effective AML induction regimen, NCCN leukemia risk predicts survival better than age in our population, and high intensity regimens can be justified in selected older patients.

Idelalisib-induced colitis and skin eruption mimicking graft-versus-host disease.

INTRODUCTION: Idelalisib is a selective inhibitor of the delta isoform of phosphatidylinositol 3-kinase which was approved by the United States Federal Drug Administration in 2014 for the treatment of relapsed chronic lymphocytic leukemia and indolent non-Hodgkin lymphoma. Drug-induced injury of the gastrointestinal tract is a relatively frequent but usually under-recognized disease entity. CASE PRESENTATION: We report the case of a 56-year-old male with a history of relapsed follicular lymphoma status post allogenic bone marrow transplant who developed severe diarrhea with a skin eruption mimicking graft-versus-host disease (GVHD) 6 months after starting idelalisib. He underwent a colonoscopy demonstrating a grossly normal-appearing colon and terminal ileum. Biopsies taken during the procedure revealed mild active ileitis, colitis, and proctitis with frequent epithelial apoptosis, and focal intra-epithelial lymphocytosis. Skin biopsies revealed sub-acute spongiotic dermatitis suggestive of either contact dermatitis or an eczematous drug reaction. Symptoms were attributed to idelalisib given their resolution with withdrawal of the drug in conjunction with the skin and colonic biopsies. CONCLUSION: High clinical suspicion and awareness of the histological features of idelalisib-associated colitis is important to distinguish it from potential mimickers such as GVHD and infectious colitis.

Narrowing down the common deleted region of 5q to 6.0 Mb in blastic plasmacytoid dendritic cell neoplasms.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematologic malignancy. Simple and complex recurrent cytogenetic abnormalities have been reported, which demonstrate predominantly genomic losses, of which deletions of 5q are the most frequent aberrations in BPDCN with or without cutaneous manifestation; however, the gene responsible for the disease remains unknown. Using microarray-based molecular characterization, a recent study on several cases of BPDCN with the 5q deletion identified a large, common deleted region (CDR) of 29 Mb that contains several possible candidate genes. We report on a 67-year-old female patient who presented with leukemic BPDCN without skin involvement and had a deletion of 5q and a t(6;8)(p21;q24). By oligo-array-comparative genome hybridization (a-CGH) method, the genomic coordinations of the 5q deletion demonstrated unique breakpoints reported for the first time. Through mapping with those published cases using the same a-CGH method, the CDR was reduced from 29 Mb to 6 Mb, which excluded the previous candidate genes and highlighted an excellent biological gene: the HINT1 gene. Moreover, a molecular cytogenetic characterization of the translocation t(6;8) was performed in search for a novel gene fusion that could be associated with tumor progression.

High-Dose Interleukin-2 (HD IL-2) Therapy Should Be Considered for Treatment of Patients with Melanoma Brain Metastases.

A retrospective review was performed on patients with stable melanoma brain metastases treated with HD IL-2 therapy (720,000 IU/kg per dose intravenously; 14 doses, 2 cycles per course, maximum 2 courses) from January 1999 to June 2011 at Saint Louis University. There were 5 men and 3 women; median age was 52.2 years (26.8-61.1 years). One patient started treatment with lung lesions only (after resection of melanoma brain disease) and experienced partial response. Seven patients had brain metastases at treatment initiation. Median overall survival (mOS) for entire cohort (n = 8) was 8.7 months (2.1 to 19.0 months). All patients with brain metastases at first dose (n = 7) showed progressive disease; mOS was 6.7 months (range 2.1-18.2 months) for this group. Patients received radiosurgery and whole brain radiation before and after HD IL-2 therapy. One patient had symptoms suggestive of neurotoxicity. A history of alcohol abuse was revealed during admission. The patient's symptoms improved with initiation of an alcohol withdrawal protocol. In this analysis, patients with melanoma brain metastases received HD IL-2 without treatment-related mortality. We think that HD IL-2 should be considered as a treatment option in patients with melanoma brain metastases who are otherwise eligible for therapy.

Active Shingles Infection as Detected on (18)F-FDG PET/CT.

We present the case of a 56-year-old male with a history of recurrent follicular lymphoma undergoing chemotherapy with multiple (18)F-FDG PET-CT studies at an outside facility. He developed a painful erythematous, pruritic rash in the left back requiring a visit to the emergency room. He was diagnosed and treated for Varicella zoster infection. He then presented to our imaging center 2 months later for a follow up (18)F-FDG PET/CT study. Imaging demonstrated a cutaneous band of increased metabolic activity in the upper back following a dermatomal distribution. This was confirmed to be in the same area as the treated Varicella zoster eruption. A subsequent follow up (18)F-FDG PET-CT scan 4 months later to confirm tumor resolution demonstrated the abnormal band of uptake in the back had resolved. This case illustrates the significance of being aware of this entity and to distinguish it from metastasis, especially in patients with a known history of malignancy.

Modified array-based comparative genomic hybridization detects cryptic and variant PML-RARA rearrangements in acute promyelocytic leukemia lacking classic translocations.

Acute promyelocytic leukemia (APL) is typically defined at the molecular level by a reciprocal translocation of the promyelocytic leukemia (PML) and retinoic acid receptor α (RARA) genes. An accurate diagnosis of APL is critical for appropriate choice of therapy and prognostic assessment. Cryptic and variant rearrangements in APL are discoverable by a variety of molecular methods including fluorescence in situ hybridization (FISH), reverse transcriptase polymerase chain reaction, or gene sequencing. Rare reports of FISH-negative APL harboring cryptic rearrangements of PML-RARA detected by reverse transcriptase polymerase chain reaction or sequencing have been described. Here, we describe the detection of cryptic or variant PML-RARA rearrangements by translocation-based comparative genomic hybridization (tCGH), a recently described modification of traditional CGH technology that facilitates the detection of balanced translocations by means of the linear amplification of a potential translocation breakpoint region(s), in 2 unusual cases of APL. One tumor lacked detectable t(15;17) by karyotype and FISH, and the other tumor lacked the typical morphologic and immunophenotypic features of APL and had a variant 3-way translocation involving PML and RARA. PML-RARA translocations were identified by tCGH in both cases providing confirmation of the diagnosis of APL. These data emphasize the benefit of using complementary molecular methods including tCGH for detecting cryptic and variant PML-RARA translocations in unusual cases of APL.

"Hyper-warburgism," a cause of asymptomatic hypoglycemia with lactic acidosis in a patient with non-Hodgkin's lymphoma.

CONTEXT: In cancer cells, the Warburg effect is defined as the avid consumption of glucose through the glycolytic pathway with concomitant lactate production, even under aerobic conditions. CASE: We report a 64-yr-old woman who was referred to our institution for pancytopenia and hypoglycemia. Physical examination demonstrated hepatosplenomegaly and petechiae. She had no clinical manifestation of neuroglycopenia, despite serum glucose of 26 mg/dl (1.4 mmol/liter) and serum lactate of 28.5 mmol/liter (normal range, 0.5-3.4 mmol/liter). Bone marrow biopsy demonstrated diffuse large B-cell lymphoma. Staging (18)F-fluorodeoxyglucose (FDG)-positron emission tomography/computed tomography showed increased FDG avidity in an enlarged spleen and absent FDG uptake in the brain. Despite dextrose infusions up to 30 g/h, there was no increase in serum glucose, but there was a paradoxical increase in serum lactate. Immunochemotherapy improved the hematological and metabolic abnormalities. Follow-up FDG-positron emission tomography/computed tomography showed a decrease in splenic avidity and an increase in brain FDG avidity. The patient refused further chemotherapy and died 1 wk after discharge. METHODS: Literature review of cases of lymphoma with lactic acidosis, with and without hypoglycemia, demonstrated that these combinations occurred in multiple categories of B- and T-cell lymphoma. There was no difference in the mortality rate in those with (75%) or without (74%) concomitant hypoglycemia. CONCLUSION: This case represents an exaggerated Warburg effect, or "hyper-warburgism," characterized by excessive lactate production and overwhelming glucose consumption. We speculate that the decreased brain FDG uptake, despite the lack of neuroglycopenic symptoms, supports the hypothesis that lactate served as a fuel for the brain, thus protecting against hypoglycemia.

Heparin-induced thrombocytopenia and cerebral venous sinus thrombosis: case report and literature review.

BACKGROUND: Heparin-induced thrombocytopenia (HIT)-related cerebral venous sinus thrombosis (CVST) has been described in 10 prior case reports in the English language medical literature. We report the first case of low molecular weight HIT-related CVST with detailed clinical course and novel therapeutic approach. METHODS: A 69-year-old woman presented with a focal seizure after total hip replacement. Enoxaparin for venous thromboembolism prophylaxis had been initiated 8 days prior to the seizure. RESULTS: The patient experienced progressive neurologic deterioration, and MRI and CT angiography were consistent with cerebral sinus thrombosis (CVST). The new onset of thrombocytopenia, thrombosis, and positive heparin ELISA (enzyme-linked immunosorbent assay) and SRA (serotonin release assay) assays confirmed HIT. In spite of aggressive management of HIT-related CVST, including argatroban therapy and endovascular mechanical thrombolysis, the patient expired. CONCLUSIONS: A review of the previous 10 case reports in the literature confirms that HIT-related CVST is often a fatal condition, particularly when diagnosed in comatose patients. Because the diagnosis is rare and often delayed relative to initial presentation, prevention is the key to improve patient outcomes. Newer anticoagulants with different mechanism of action than heparin are currently under review by the FDA; they will facilitate prevention of HIT-related CVST and other HIT-related neurological complications.

C-MOPP: the forgotten regimen plus Rituximab for untreated and relapsed follicular lymphoma.

C-MOPP is a chemotherapy regimen for the treatment of Non-Hodgkin lymphoma (NHL). Because rituximab improves results in B-cell NHL, we added rituximab to C-MOPP, giving it the term C-MOPP-R. We retrospectively report the results of C-MOPP-R treatment for follicular lymphoma at Saint Louis University Cancer Center from 2000-2009. Treatment response was assessed with fusion PET/CT using International Harmonization Project Criteria and toxicity using National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0. Thirty-seven patients with follicular lymphoma were treated at our institution with C-MOPP-R. The complete response rate was ninety-four percent and sixty-eight percent in untreated and relapsed patients, respectively. The median progression-free and overall survivals were not reached with median observation time of 34 months. Development of peripheral neuropathy required truncation of planned vincristine dosing in nearly half of patients. We believe that C-MOPP-R results in excellent response rates, progression-free, and overall survival for untreated and relapsed follicular lymphoma and capped vincristine dosing is essential to optimize safety.